Different COVID-19 vaccines induce distinct reprogramming of stromal functions in draining lymph nodes

The non-leukocytic stromal cells of lymph nodes critically regulate immune responsiveness. However, the effects of different SARS-CoV-2 vaccines on stromal cell biology are unknown. We used single-cell transcriptomics to study early responses of stromal cells in draining lymph nodes after immunizing mice with clinically used COVID-19 vaccines, namely Spikevax®, Comirnaty®, Vaxzevria® and Nuvaxovid™. We found that vaccinations lead to robust transcriptomic changes, including vaccine-selective ones, in the different lymph node stromal cell populations priming the lymph node for the upcoming adaptive immune response. Mice were immunized with COVID-19 vaccines and the draining lymph node stromal cells were isolated with enzymatic digestion. Non-hematopoietic cells were enriched using magnetic beads and the negative fraction, i.e. stromal cells was subjected for droplet-based scRNA-seq.